Identification of novel bifunctional calmodulin-binding and microtubule-stabilizing motifs in STOP proteins
Identification of novel bifunctional calmodulin-binding and microtubule-stabilizing motifs in STOP proteins
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DOI：
10.1074/jbc.m011614200
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发表时间：
2001-08-17
影响因子：
4.8
通讯作者：
Jot, D
中科院分区：
文献类型：
--
作者：
Bosc, C;Frank, R;Jot, D
尽管微管是本质上不稳定的微管蛋白组件，但许多细胞类型含有稳定的聚合物，可以抵抗解聚条件，例如暴露于寒冷或药物诺考达唑。这种微管稳定性很大程度上是由于聚合物与 STOP 蛋白的结合。 STOP 变体有多种，其中一些能够诱导微管对冷和诺考达唑产生抗性，另一些仅具有微管冷稳定活性。 STOP 蛋白的这些微管稳定作用受到钙调蛋白的抑制，我们现在证明它们是由两种不同类型的重复模块序列（Mn 和 Me）决定的，两者都含有钙调蛋白结合肽，但显示出不同的微管稳定活性。当锰模块在细胞中表达时，会诱导微管对寒冷和诺考达唑产生抗性。 Me 模块对应于 STOP 中央重复序列，仅具有微管冷稳定活性。小鼠神经元 STOP 包含三个 Mn 模块和四个 Me 模块，可诱导细胞微管的寒冷和耐药性。与神经元 STOP 相比，非神经元 F-STOP 缺乏多个 Mn 模块，这对应于无法诱导诺考达唑耐药。 STOP 模块代表了新型双功能钙调蛋白结合和微管稳定序列，这可能对于细胞中观察到的不同微管稳定模式的生成至关重要。
Although microtubules are intrinsically labile tubulin assemblies, many cell types contain stable polymers, resisting depolymerizing conditions such as exposure to the cold or the drug nocodazole. This microtubule stabilization is largely due to polymer association with STOP proteins. There are several STOP variants, some with capacity to induce microtubule resistance to both the cold and nocodazole, others with microtubule cold stabilizing activity only. These microtubule-stabilizing effects of STOP proteins are inhibited by calmodulin and we now demonstrate that they are determined by two distinct kinds of repeated modular sequences (Mn and Me), both containing a calmodulin-binding peptide, but displaying different microtubule stabilizing activities. Mn modules induce microtubule resistance to both the cold and nocodazole when expressed in cells. Me modules, which correspond to the STOP central repeats, have microtubule cold stabilizing activity only. Mouse neuronal STOPs, which induce both cold and drug resistance in cellular microtubules, contain three Mn modules and four Me modules. Compared with neuronal STOPs, the non-neuronal F-STOP lacks multiple Mn modules and this corresponds with an inability to induce nocodazole resistance. STOP modules represent novel bifunctional calmodulin-binding and microtubule-stabilizing sequences that may be essential for the generation of the different patterns of microtubule stabilization observed in cells.